CaMKII binding to GluN2B is critical during memory consolidation
CaMKII binding to GluN2B is critical during memory consolidation
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CaMKII 与 GluN2B 的结合在记忆巩固过程中至关重要
DOI：
10.1038/emboj.2011.482
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发表时间：
2012-03-07
期刊：
影响因子：
11.4
通讯作者：
Hell, Johannes W.
中科院分区：
文献类型：
--
作者：
Halt, Amy R.;Dallapiazza, Robert F.;Hell, Johannes W.
记忆对于我们正常的日常生活以及自我认知至关重要。钙离子通过N - 甲基 - D - 天冬氨酸型谷氨酸受体（NMDA受体）内流，以及随之引发的钙离子和钙调蛋白依赖性蛋白激酶（CaMKII）的激活，是记忆形成及其生理关联——长时程增强（LTP）所必需的。钙离子内流促使CaMKII与NMDA受体结合，从而有策略地将CaMKII募集到正在发生增强的突触处。我们培育出了带有两个点突变的小鼠，这些突变会削弱CaMKII与NMDA受体GluN2B亚基的结合。对于CaMKII而言，钙离子触发的突触后积累在很大程度上被消除，而对于锚定α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸型谷氨酸受体（AMPA受体）的跨膜AMPAR调节蛋白（TARPs）来说，其稳定性也受到破坏。LTP降低了50%，并且CaMKII对AMPA受体GluA1亚基的磷酸化（该磷酸化可增强AMPA受体的电导）也受到损害。突变小鼠在莫里斯水迷宫（MWM）实验中的学习能力与野生型小鼠相当，但在早期记忆巩固阶段的回忆过程中表现出缺陷。因此，CaMKII与NMDA受体受活动驱动的相互作用，对于训练后最早24小时（而非1 - 2小时）MWM记忆的回忆很重要，这可能是由于巩固过程受损所致。《欧洲分子生物学组织杂志》（2012年），31卷，1203 - 1216页。doi: 10.1038/emboj.2011.482；2012年1月10日在线发表
Memory is essential for our normal daily lives and our sense of self. Ca2+ influx through the NMDA-type glutamate receptor (NMDAR) and the ensuing activation of the Ca2+ and calmodulin-dependent protein kinase (CaMKII) are required for memory formation and its physiological correlate, long-term potentiation (LTP). The Ca2+ influx induces CaMKII binding to the NMDAR to strategically recruit CaMKII to synapses that are undergoing potentiation. We generated mice with two point mutations that impair CaMKII binding to the NMDAR GluN2B subunit. Ca2+-triggered postsynaptic accumulation is largely abrogated for CaMKII and destabilized for TARPs, which anchor AMPA-type glutamate receptors (AMPAR). LTP is reduced by 50% and phosphorylation of the AMPAR GluA1 subunit by CaMKII, which enhances AMPAR conductance, impaired. The mutant mice learn the Morris water maze (MWM) as well as WT but show deficiency in recall during the period of early memory consolidation. Accordingly, the activity-driven interaction of CaMKII with the NMDAR is important for recall of MWM memory as early as 24h, but not 1-2h, after training potentially due to impaired consolidation. The EMBO Journal (2012) 31, 1203-1216. doi: 10.1038/emboj.2011.482; Published online 10 January 2012